This project seeks to develop new statistical tools for evaluating gene-environment interactions and genetic susceptibility. Work has proceeded in the area of improving study designs and associated techniques for data analysis. Geneticists have proposed using cases and their parents (case-parents triads) to study genetic effects on disease risk while overcoming the problem of population stratification or admixture. If a population consists of a number of distinct subpopulations that differ in baseline disease rates and in the frequency of a genetic variant, case-control studies may find associations between the variant and disease that arise simply because of the differing characteristics of the subpopulations. Such associations lack etiologic import. Case-parents triad designs can eliminate such potentially misleading associations. We are investigating designs that augment case-parents triads with control-parents triads to overcome some shortcomings of using case-parents triads alone. Such designs should more fully extend protection against population structure to studies of genotype and exposure together.